Affiliations: Shanghai Institute of Digestive Surgery, Ruijin
Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai,
China | Department of Surgery, Shanghai Jiao Tong University
School of Medicine, Shanghai, China
Note: [] Corresponding author: Bingya Liu, M.D., PhD., Shanghai Key
Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of
Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University,
Shanghai 200025, China. Tel.: +86 21 64674654;
Fax: +86 21 64373909; E-mail: byliu@sjtu.edu.cn
Abstract: Most cases of gastric cancer (GC) are not diagnosed at early stage
which can be curable, so it is necessary to identify effective biomarkers for
its diagnosis and pre-warning. We have used methylated DNA immunoprecipitation
(MeDIP) to identify genes that are frequently methylated in gastric cancer cell
lines. Promoter regions hypermethylation of candidate genes were tested by
methylation-specific polymerase chain reaction (MSP) in serum samples,
including GC (n=58), gastric precancerous lesions (GPL, n=46), and normal
controls (NC, n=30). Eighty two hypermethylated genes were acquired by array
analysis and 5 genes (BCAS4, CHRM2, FAM5C, PRAC and MYLK) were
selected as the candidate genes. Three genes (CHRM2, FAM5C and
MYLK) were further confirmed to show methylation rates increased with
progression from NC to GPL, then to GC. There was obvious decrease in detection
of FAM5C and MYLK hypermethylation, but not CHRM2, from
preoperative to postoperative evaluation (P< 0.001). Combined detection of
FAM5C and MYLK hypermethylation had a higher sensitivity in GC
diagnosis (77.6%,45/58) and pre-warning (30.4%,14/46) than one single
gene detection and also had a high specificity of 90%. The combined
hypermethylated status of FAM5C and MYLK correlated with tumor size
(P<0.001), tumor invasion depth (P=0.001) and tumor-node-metastasis
(TNM) stage (P=0.003). Hypermethylated FAM5C and MYLK can be
used as potential biomarkers for diagnosis and pre-warning of GC.
